Circadian disruption in diseases: an approach from enhancer genetics
Shinpei Kawaoka
Coordinated circadian gene expression is critical for maintaining homeostasis. Indeed, expression rhythm of various genes is disrupted in diseases. For example, we recently reported that remote solid cancers cause circadian disruption in the liver. Yet, which altered rhythm is causal for diseases remains poorly investigated. This is largely due to the technical difficulty in manipulating rhythm of a specific gene in vivo. We tackle this problem using enhancer genetics. Enhancers are non-coding DNAs that determine spatiotemporal gene expression patterns. Deletion of an enhancer, when appropriately done, enables us to ablate a specific gene expression program in vivo. In this talk, utilizing enhancer genetics, I will demonstrate that disruption in a single oscillatory gene can be a cause of diseases. I hope that this talk will convince the audience regarding the strengths of enhancer genetics and the importance of circadian biology at the single rhythm level.
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